The mechanism of the Ni-catalyzed reductive cross-coupling reaction of bromobenzene (R1) and methyl 4-bromobenzoate (R2) to form an unsymmetrical biaryl system has been theoretically investigated using density functional theory calculations. Our results showed that the Ni0-catalyzed process was favored over the NiI-catalyzed mechanism. The mechanism for the reaction of the Ni0 catalyst initially attacking either R1 or R2 was quite similar, where the energy barrier in the gas phase for the rate-limiting step was 70.50 or 49.66 kJ·mol-1, respectively. The mechanism in the favored Ni0-catalyzed reaction involved the following steps: first oxidative addition, reduction, second oxidative addition, reductive elimination, and catalyst regeneration. Our calculated results also indicated that no organometallic reagents were produced in the reaction cycle.